Immune Netw.  2017 Feb;17(1):13-19. 10.4110/in.2017.17.1.13.

The Specific Roles of Vitamins in the Regulation of Immunosurveillance and Maintenance of Immunologic Homeostasis in the Gut

• Hosomi K
• Kunisawa J

• KMID: 2368972
• DOI: http://doi.org/10.4110/in.2017.17.1.13

Abstract

Vitamins are micronutrients which are essential for the maintenance of biological responses including immune system. Hence, vitamin deficiency increases a risk of infectious, allergic, and inflammatory diseases. Accumulating evidence has recently revealed the molecular and cellular mechanisms of vitamin-mediated regulation in the active and quiescent immune responses. In this review, we focus on the immunologic roles of vitamins in the regulation of homeostasis and surveillance in the gut.

Keyword

Vitamin; IgA; Inflammation; Regulatory T cell; Energy metabolism

MeSH Terms

Avitaminosis
Energy Metabolism
Homeostasis*
Immune System
Immunoglobulin A
Inflammation
Micronutrients
Monitoring, Immunologic*
Vitamins*
Immunoglobulin A
Micronutrients
Vitamins

Figure

• 

  Figure 1 Pivotal roles of vitamins in the maintenance of immunologic homeostasis in the gut. Vitamin A-derived retinoic acid promotes the differentiation of naive T cells to Treg cells and simultaneously inhibits the induction of Th17 cells in the steady state. Like retinoic acid, Vitamin D (as an active form1α,25-dihydroxyvitamin D3) inhibits the production of pro-inflammatory cytokines such as IFN-γ, IL-17 and IL-21 from T cells together with the promoted differentiation of Treg cells. It also prevents differentiation and maturation of DCs and increases the expression of tight junction protein such as claudins in the epithelial cells. Upon the differentiation of Treg cells, they express high levels of vitamin B9 receptor (folate receptor 4, FR4), which essential for their survival. α-tocopherol, an isoform of vitamin E, can inhibit T cell infiltration into intestine through the negative regulation of signal transduction from VCAM-1 and ICAM-1 by antagonizing protein kinase C.

• 

  Figure 2 Various roles of vitamins in the regulation of gut immunity. Vitamin A is converted to retinoic acid by retinal dehydrogenases (RALDH) expressing dendritic cells in the Peyer's patches, which induces the expression of gut homing molecules (α4β7 integrin and CCR9) on antigenprimed cells (e.g., IgA+ B cells) and allows them to traffic into the intestinal lamina propria. In the lamina propria, IgA+ B cells differentiate into IgA-producing plasma cells. IgA is then transported into the intestinal lumen, where it binds to pathogens to inhibit their invasion and function. Vitamin B1 is essential for energy metabolism, especially maintenance of TCA cycle, and therefore associates with maintenance of naive B cells which utilize predominantly TCA cycle for energy generation. Vitamin B2 also involves in the energy metabolism of immune cells. In addition, bacterial metabolite of vitamin B2 activates mucosal associated invariant T (MAIT) cells via the presentation by major histocompatibility complex (MHC) related protein MR1. Vitamin D enhances production of antimicrobial peptides from Paneth cells and macrophages via vitamin D receptor, which provides an additional immunosurveillance system.

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